Abstract
Potassium channels play important roles in vital cellular signaling processes in both excitable and nonexcitable cells. Over 50 human genes encoding various K+ channels have been cloned during the past decade, and precise biophysical properties, subunit stoichiometry, channel assembly, and modulation by second messenger and ligands have been elucidated to a large extent. Recent advances in genetic linkage analysis have greatly facilitated the identification of many disease-producing loci, and naturally occurring mutations in various K+ channels have been identified in diseases such as long-QT syndromes, episodic ataxia/myokymia, familial convulsions, hearing and vestibular diseases, Bartter's syndrome, and familial persistent hyperinsulinemic hypoglycemia of infancy. In addition, changes in K+ channel function have been associated with cardiac hypertrophy and failure, apoptosis and oncogenesis, and various neurodegenerative and neuromuscular disorders. This review aims to 1) provide an understanding of K+ channel function at the molecular level in the context of disease processes and 2) discuss the progress, hurdles, challenges, and opportunities in the exploitation of K+ channels as therapeutic targets by pharmacological and emerging genetic approaches.
Footnotes
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↵1 Address for correspondence: Char-Chang Shieh, Ph.D., Dept. 47C, Bldg. AP9A 3rd Floor, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064. E-mail:char-chang.shieh{at}abbott.com
- The American Society for Pharmacology and Experimental Therapeutics
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